Anti-RANKL Antibody For Active Charcot Foot Neuro-Osteoarthropathy in Patients with Diabetes and Chronic Kidney Disease.

ABSTRACT

BACKGROUND: Charcot neuroosteoarthropathy (CNO) is characterized with increased osteoclastic activity that can be curbed with antiresorptive agents. Chronic kidney disease (CKD) precludes bisphosphonates but anti-receptor activator of nuclear factor-B ligand (anti-RANKL) antibody, denosumab, can be contemplated in CKD. We investigated denosumab for active CNO of foot in CKD for CNO remission. METHODS: During the study period, 446 persons of diabetes with unilateral, active CNO of foot and CKD were identified and 78 were finally enrolled. Patients received either 60 mg denosumab (single-dose, subcutaneous) along with standard of care (SoC) as total contact cast (TCC) (group A; n = 26) or SoC (group B; n = 52) only. Patients were followed every 4 weeks until CNO remission and subsequently every 8 weeks until 48 weeks following remission. Remission was defined as temperature difference <2 °C between 2 feet confirmed twice (4 weeks apart) with clinical resolution of signs of inflammation. The primary outcome studied was proportion of patients achieving remission within 48 weeks and the time to remission. RESULTS: Median age was 56.5 (48.8-65) and 57 (48.5-61.2) years, P = .57; duration of diabetes 16 (10-25.3) and 14.9 (10-19) years, P = .151; and estimated glomerular filtration rate 44.8 (21.1-65.6) and 45.7 (32.9-55.7) mL/min/1.73 m2, P = .771, in group A and B, respectively. Median temperature difference at presentation between the affected and opposite foot was 3.4 °C (2.7-6.9) and 3.2 °C (2.2-4.0), P = .119, respectively. All patients achieved remission in group A (100%) compared with 42 (80.8%) in group B (P = .006) (hazard ratio 0.52, 95% CI 0.32-0.87; P = .012). The median time to remission was similar in the 2 groups (15 [11-25] and 17.5 [14-31.5] weeks, P = .229, respectively). 25-Hydroxyvitamin D3 >14 ng/mL was significantly associated (OR 9.5, 95% CI 1.04-87.5, P = .045) with remission. CONCLUSION: Anti-RANKL antibody added to SoC (TCC) induces remission of active foot CNO in greater proportions of patients with diabetes and CKD.